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Author Notes:

Correspondence: Asha Moudgil Email: amoudgil@childrensnational.org

The authors would like to thank Federica Alessi and Luna Zaru for their statistical expertise.

The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation.

Vidya Perera, Bindu Murthy, Mustimbo E. Roberts, and Martin S. Polinsky are salaried employees of and own stock in Bristol‐Myers Squibb.

Subjects:

Research Funding:

This study was funded by Bristol‐Myers Squibb.

Support for third‐party writing assistance for this manuscript was provided by Tiffany DeSimone, PhD, of CodonMedical, an Ashfield Company, part of UDG Healthcare plc, and was funded by Bristol‐Myers Squibb.

Asha Moudgil has received research funding from Bristol‐Myers Squibb.

Vikas R. Dharnidharka has received consulting fees from Bristol‐Myers Squibb and Atara Biotherapeutics and grant support from Bristol‐Myers Squibb.

Daniel I. Feig has received research funding from Bristol‐Myers Squibb and Relypsa.

Barry L. Warshaw has received research funding from Bristol‐Myers Squibb.

Robert B. Ettenger has received grant support from Bristol‐Myers Squibb, Veloxis, and Novartis, and a travel grant from Novartis.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Surgery
  • Transplantation
  • belatacept
  • clinical research
  • practice
  • immunosuppressant - fusion proteins and monoclonal antibodies
  • kidney transplantation
  • nephrology
  • living donor
  • pharmacokinetics
  • pharmacodynamics
  • simulation
  • CALCINEURIN INHIBITOR
  • CYCLOSPORINE
  • SURVIVAL
  • OUTCOMES
  • CHILDREN
  • REGIMEN
  • SAFETY
  • AGE

Phase I study of single-dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients

Tools:

Journal Title:

American Journal of Transplantation

Volume:

Volume 19, Number 4

Publisher:

, Pages 1218-1223

Type of Work:

Article | Final Publisher PDF

Abstract:

Belatacept is an intravenously infused selective T cell costimulation blocker approved for preventing organ rejection in renal transplant recipients aged ≥18 years. This phase I trial examined the pharmacokinetics and pharmacodynamics (percentage CD86 receptor occupancy [%CD86RO]) of a single dose of belatacept (7.5 mg/kg) administered to kidney transplant recipients aged 12-17 years receiving a stable calcineurin inhibitor–based immunosuppressive regimen. Nine adolescents (mean age 15.1 years) who were seropositive for Epstein-Barr virus were enrolled; all completed the 6-month study. Pharmacokinetics suggested relatively low variability of exposure (coefficients of variation for maximum observed serum concentration [C max ] and area under the serum concentration-time curve from time zero extrapolated to infinity [AUC 0-INF ] were 20% and 25%, respectively). Mean half-life (T 1/2 ) occurred 7.2 days postinfusion. Belatacept total body clearance was 0.48 mL/h/kg, and volume of distribution at steady-state (V ss ) was low at 0.09 L/kg. Compared with historical data from healthy adult volunteers administered a single dose of belatacept 10 mg/kg and adult kidney transplant recipients administered multiple doses of belatacept 5 mg/kg, pharmacokinetic values for adolescents were similar, indicating consistency across adolescent and adult populations. Mean %CD86RO increased with increasing belatacept concentration, indicating a direct relationship between pharmacokinetics and pharmacodynamics. Four patients reported 7 serious adverse events; none was considered related to belatacept. These data will inform belatacept dose selection in future studies of adolescent kidney transplant recipients.

Copyright information:

© 2018 The Authors American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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